Scope: Cholecalciferol (D3) and retinyl palmitate (RP) are the two main fat-soluble vitamins found in foods from animal origin. It is assumed that they are solubilized in mixed micelles prior to their uptake by intestinal cells but only scarce data are available on the relative efficiency of this process and on the physicochemical parameters that govern it. Methods: The solubility of D3 and RP in synthetic mixed micelles composed of bile lipids, sodium taurocholate (NaTC) and lipid digestion products was measured by HPLC. Surface tension and surface pressure-surface area measurements of vitamin and mixed micelle monolayers, alone or in combination, were performed to analyze the interactions between these components. Results: Mixture of lipids and NaTC allowed formation of micelles with higher molecular order at lower concentrations than pure NaTC molecules. D3 solubilization in mixed micelle solutions was several times higher than that of RP. NaTC and mixed lipids interacted better with a D3 monolayer than with a RP one. Furthermore, D3 showed some self-association properties in aqueous solution. Conclusions: Solubilization efficiency of D3 in an aqueous phase rich in mixed micelles is several times higher than that of RP because D3 is incorporated into NaTC and lipid domains much more efficiently than RP, and because it is able to self-aggregate in soluble micelle-like structures.